This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rowlands, C. Articles by Langdon, S. Search for Related Content PubMed PubMed Citation Articles by Rowlands, C. Articles by Langdon, S.

Characterization of the Aryl Hydrocarbon Receptor and Aryl Hydrocarbon Responsiveness in Human Ovarian Carcinoma Cell Lines¹

Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, Texas 77843-4466 [C. R., V. K., X. W., M. S., S. S.], and ICRF Medical Oncology Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU Scotland [W. R. M., S. L.]

The human ovarian carcinoma cell lines PE01, PE04, and PE06 express the estrogen receptor and studies with the PE04 cells have shown that tamoxifen inhibits 17ß-estradiol-induced proliferation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a broad spectrum antiestrogen which works through the aryl hydrocarbon receptor. Incubation of the three cell lines with [³H]TCDD followed by isolation of nuclear extracts showed that the PE01, PE04, and PE06 cells express the aryl hydrocarbon receptor (23 to 87 fmol/mg protein) which exhibits sedimentation properties (7.5 to 7.9 S) on sucrose gradients similar to that observed in other mammalian species. Aryl hydrocarbon responsiveness was determined by the induction of P4501A1 mRNA levels and ethoxyresorufin O-deethylase activity by TCDD. Induction of both parameters was observed only in the PE04 cells. Gel mobility shift assays with a consensus dioxin-responsive element (DRE, 26-mer) showed that after incubation of the nuclear extracts from the 3 cell lines with ³²P-DRE a retarded band formed only with nuclear receptor complex from PE04 cells. 17ß-Estradiol stimulated proliferation of the PE04 and PE06 but not the PE01 cells; 1 nM TCDD alone either did not affect or inhibited the growth of these cells and 1 nM TCDD significantly inhibited the 17ß-estradiol-induced proliferation of the PE04 and PE06 cells. Treatment of the PE04 cells with 1 nM 17ß-estradiol resulted in a time-dependent enhanced secretion of the M_r 52,000 protein (procathepsin D) and, after 48 h, a 51% increase in the secretion of this protein was observed. Cotreatment of the PE04 cells with 0.1 or 1.0 nM TCDD completely inhibited the 17ß-estradiol-induced secretion of the M_r 52,000 protein. These data show that TCDD exhibits antiestrogenic activity in estrogen receptor-positive ovarian carcinoma cell lines; however, in the PE06 cells, there was no correlation between the effects of TCDD on the induction of CYP1A1 gene expression and the results of the gel shift assay (i.e., nonresponsiveness) versus the observed antiestrogenic activity.

¹ This work was supported in part by NIH Grant ES04176. S. S. is a Burroughs Wellcome Toxicology Scholar.

² To whom requests for reprints should be addressed.

Received 6/30/92. Accepted 2/10/93.

This article has been cited by other articles:

				A. J M O'Donnell, K. G Macleod, D. J Burns, J. F Smyth, and S. P Langdon Estrogen receptor-{alpha} mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen Endocr. Relat. Cancer, December 1, 2005; 12(4): 851 - 866. [Abstract] [Full Text] [PDF]